Navigation Links
Stem cell research leads to potential new therapy for rare blood disorder

A unique partnership between industry and academia has led to human clinical trials of a new drug for a rare class of blood diseases called myeloproliferative disorders (MPD), which are all driven by the same genetic mutation and can evolve into leukemia. In just one year, collaborative discoveries by stem cell researchers from the University of California, San Diego, Dana-Farber Cancer Institute, the Mayo Clinic and a San Diego pharmaceutical company, TargeGen, moved from identification of the most promising drug candidate to clinical trials for a new drug to fight this degenerative blood disorder, which affects more than 100,000 Americans.

A study headed by Catriona H.M. Jamieson, M.D. Ph.D., assistant professor of medicine at the University of California, San Diego and Director for Stem Cell Research at Moores UCSD Cancer Center, found an inhibitor that can stop the over-proliferation of blood cells that results in problems with blood clotting, heart attacks and, in some cases, leukemia. Funded in part by a grant from the California Institute for Regenerative Medicine (CIRM), the study will be published in Cancer Cell on April 8, 2008. A parallel study at Harvard Medical School, headed by D. Gary Gilliland, Ph.D., M.D., yielded similar results which will appear in the same issue of Cancer Cell.

As a clinician, I asked myself who is going to get this disease, and what can we do to stop its progression, instead of waiting until it evolves into a deadly cancer? said Jamieson. This project has been so extraordinary, because a small pharmaceutical company took a big chance on a rare disease.

With major contributions from collaborators Jason Gotlib at Stanford University and Ayalew Tefferi at the Mayo Clinic, the research findings led to development of the inhibitor by TargeGen. That drug is currently being tested in human clinical trials at the UC San Diego School of Medicine, the Mayo Clinic, M.D. Anderson Cancer Center, and the University of Michigan, Stanford and Harvard University Schools of Medicine.

A patient with MPD makes too many blood cells, caused by a mutation expressed in the stem cell, the early stage cell that goes on to differentiate to become either red or white blood cells. In 2006, Jamieson was first author on a paper published in PNAS, outlining the discovery that a mutation in the JAK2 signaling pathway in patients with a type of MPD called polycythemia vera (PV) allows cells to bypass the process which would normally regulate the production of red blood cells. As a result of this defect, the bone marrow produces excessive numbers of red blood cells.

In the current research described in Cancer Cell, the UCSD School of Medicine researchers and collaborators transferred human cord blood stem cells, engineered to contain the mutant JAK2 gene, into mouse models with a suppressed immune system to find whether over-expression of a single gene could drive, or initiate, the disease. These stem cells were introduced directly into the liver, the main site of blood development in the newborn mouse. As a result, the stem cells over-expressing the mutant gene led to overproduction of human red blood cells, and the mice developed a disease that looked like PV.

The researchers corroborated these results by injecting actual stem cells from patients with PV into the same mouse model, achieving similar results. We found that the JAK2 mutation was necessary and sufficient, by itself, to drive the disease, Jamieson said.

Theorizing that blocking this mutation would prevent overproduction of red blood cells, TargeGen developed a selective JAK2 inhibitor called TG101348. This therapy was shown in animal studies to halt over-expression of the gene and reverse excessive production of red blood cells. Because TG101348 selectively targets the JAK2 protein that causes the disease, side effects have been minimized.

Pre-clinical testing at the UCSD and Harvard University Schools of Medicine confirmed the therapeutic potential of TG101348. The compound was rapidly advanced into the current, ongoing human clinical trials being conducted at major research institutions across the country, said John Hood, Ph.D., Director of Research for TargeGen. This unique industry-academia collaboration has helped guide a new drug from bench to bedside, from evaluating the compounds efficacy on cancer stem cells to its evaluation in patients bearing a disease which otherwise has very limited treatment options.


Contact: Debra Kain
University of California - San Diego

Related medicine news :

1. Childrens Hospital Contributes Genotype Data to Enhance Autism Research Worldwide
2. Animal research suggests new strategy for treating cocaine addiction
3. NTMir Announces First International Research Grant for Genome Sequencing
4. Clinical trial volunteers mostly indifferent -- but not blind to -- researchers financial conflicts
5. Xoft Medical Director Recognized by Gotham Prize for Cancer Research
6. Researchers learn how signaling molecule orchestrates breast cancers spread
7. Global Benchmarking Council Launches New Virtual Tour of Research & Networking Service
8. Pollin Pediatric Research Prize awarded for discovery of lifesaving treatment of RDS
9. High school students get a taste of dental research
10. Cato Research Ltd. and Advanced Targeting Systems, Inc. Partner to Develop SP-SAP for Chronic Pain
11. Diabetes Research, Advocacy and Education Gets Big Boost with Donation of Two- Year Lease for 2008 Chrysler Sebring Convertible
Post Your Comments:
(Date:11/26/2015)... ... , ... Inevitably when people think Thanksgiving, they also think Holiday sales and ... Friday and Cyber Monday massage chair sales to receive the best pricing ... to find the best massage chair deals, they can see all of the coupons ...
(Date:11/26/2015)... ... November 26, 2015 , ... Jobs in hospital medical ... professionals and offered by healthcare staffing agency Aureus Medical Group . ... of October 2015 among those searching for healthcare jobs through the company’s website, ...
(Date:11/26/2015)... ... November 26, 2015 , ... ... wellness consultation, has collaborated with Women’s Web – an online resource for ... topics on mental and emotional well-being relationship, life balance, stress, professional development, ...
(Date:11/25/2015)... ... November 25, 2015 , ... The holiday ... dish and pleasing the palates of attendees is of the utmost importance. Whether ... a seasonal get-together, give these recipes a try this holiday season. , Turkey ...
(Date:11/25/2015)... ... 2015 , ... Dr. John Pierce, Medical Director at the Ageless Forever clinic ... the Capillus272™ Pro laser therapy cap. FDA cleared for safety and efficacy, the Capillus272 ... need for surgery, prescription pills, or topical foams. , “Capillus272™ Pro is a ...
Breaking Medicine News(10 mins):
(Date:11/25/2015)... 25, 2015 On Tuesday, November 24, ... trial against Wright Medical Technology, Inc. for product ... metal-on-metal hip implant device, awarded $11 million in ... week trial and three days of deliberations, the ... was defectively designed and unreasonably dangerous, and that ...
(Date:11/25/2015)...  Trovagene, Inc. (NASDAQ: TROV ), a developer ... Officer Antonius Schuh, Ph.D., is scheduled to present a ... Jaffray Healthcare Conference. th Annual Piper ... in New York on Tuesday, ... will be available for one-on-one meetings during the conference. ...
(Date:11/25/2015)... , November 25, 2015 ... self-monitoring blood glucose devices was valued at $11,171.1 million ... a CAGR of 5.7% during 2015 - 2022. The ... and increasing prevalence of diabetes. In addition, the increase ... is also contributing to the growth of the market. ...
Breaking Medicine Technology: